title: D2-like but not D1-like dopamine receptors are involved in the ventrolateral orbital cortex-induced antinociception: a GABAergic modulation mechanism.
abstract: The ventrolateral orbital cortex (VLO) is part of an endogenous analgesic system consisting of an ascending pathway from the spinal cord to VLO via the thalamic nucleus submedius (Sm) and a descending pathway to the spinal cord relaying in the periaqueductal gray (PAG). This study examines whether activation of D(1)-like and D(2)-like dopamine receptors in VLO produces antinociception and whether GABAergic modulation is involved in the VLO, D(2)-like dopamine receptor activation-evoked antinociception. The radiant heat-evoked tail flick (TF) reflex was used as an index of nociceptive response in lightly anesthetized rats. Microinjection of the D(2)-like (D(2)/D(3)) dopamine receptor agonist quinpirole (0.1-2.0 microg), but not D(1)-like (D(1)/D(5)) receptor agonist SKF-38393 (1.0, 5.0 microg), into VLO produced dose-dependent antinociception which was antagonized by the D(2)-like (D(2)/D(3)) receptor antagonist raclopride (1.5 microg). We also found that VLO application of the GABA(A) receptor antagonist bicuculline or picrotoxin (100 ng) enhanced the quinpirole-induced inhibition of the TF reflex, whereas the GABA(A) receptor agonist muscimol (250 ng) or THIP (1.0 microg) significantly attenuated the quinpirole-induced inhibition. These results suggest that D(2)-like, but not D(1)-like, dopamine receptors are involved in VLO-induced antinociception and that GABAergic disinhibitory mechanisms participate in the D(2)-like receptor mediated effect. These findings provide support for the hypothesis that D(2)-like receptor activation may inhibit the inhibitory action of the GABAergic interneurons on the output neurons projecting to PAG leading to activation of the brainstem descending inhibitory system and depression of nociceptive inputs at the spinal dorsal horn.
authors.affiliation: Department of Physiology and Pathophysiology, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi 710061, People's Republic of China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Sheng
authors.forename: Chao-Ling
authors.initials: CL
authors.lastname: Qu
authors.forename: Fu-Quan
authors.initials: FQ
authors.lastname: Huo
authors.forename: Jian-Qing
authors.initials: JQ
authors.lastname: Du
authors.forename: Jing-Shi
authors.initials: JS
authors.lastname: Tang
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D015259:Dopamine Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism*; D018682:GABA Agents / Q000494:pharmacology; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods*; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000502:physiology*; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D015259:Dopamine Agents; D018682:GABA Agents; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D005680:gamma-Aminobutyric Acid; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine